Int. J. Pharm. Sci. Rev. Res., 22(1), Sep – Oct 2013; nᵒ 20, 98-106
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Review Article
Nanosuspension: A Review
Rupali L.Shid*, Shashikant.N.Dhole, Nilesh Kulkarni, Santosh L.Shid
Modern College of Pharmacy (For Ladies) Moshi, Pune University, India.
*Corresponding author’s E-mail: rupalishid23@gmail.com
Accepted on: 13-06-2013; Finalized on: 31-08-2013.
ABSTRACT
Solubility is the crucial factor for drug effectiveness, independence of the route of administration. Large proportions of newly
discovered drugs are water insoluble, and therefore poorly bioavailable contributing to deserted development effort. These
so‐called 'Brickellia' candidates can now be delivered by formulating them into Nanosuspension. Nanosuspension technology solved
the problem of drugs which are poorly aqueous soluble and less bioavailability. Stability and bioavailability of the drugs can be
improved by the Nanosuspension technology. Preparation of Nanosuspension is simple and applicable to all drugs which are
aqueous insoluble. Nanosuspensions are prepared by using wet mill, high pressure homogenizer, emulsion‐solvent evaporation,
melt emulsification method and super critical fluid techniques. Nanosuspension can be prepared by using stabilizers, organic
solvents and other additives such as buffers, salts, polyols, osmogent and cryoprotectant. Nanosuspensions can be delivered by oral,
parenteral, pulmonary and ocular routes. Nanosuspensions can also be used for targeted drug delivery when incorporated in the
ocular inserts and mucoadhesive hydrogels.
Keywords: Dissolution, Nanosuspension, Saturation solubility, Solubility enhancement, Surfactant.
Revaprazan,16 Aceclofenac,17
Nanosuspension .
INTRODUCTION
Nanosuspension
M
ore than 40% of the new chemical entities
being generated through drug discovery
programmes are poorly water‐soluble or
lipophilic compounds. Formulating a poorly water soluble
drug has always been a challenging problem confronted
by the pharmaceutical scientist. The formulation of
nano‐sized particles can be implemented to all drug
compounds belonging to biopharmaceutical classification
system (BCS) classes II and IV to increase their solubility
and hence partition into gastrointestinal barrier.
Micronization is used for class II drugs of (BCS), i.e. drugs
having a good permeability and poor solubility.1‐5 There
are many conventional methods for increasing the
solubility of poorly soluble drugs, which include
6
micronization, solubilization using co‐solvents, salt form,
surfactant dispersions, precipitation technique, and oily
solution. Other techniques are like liposomes, emulsions,
microemulsion,
solid dispersion
and
inclusion
complexation using cyclodextrins6-12 show sensible
achiever, but they lack in universal applicability to all
drugs. These techniques are not applicable for those
drugs which are not soluble in aqueous and organic
solvents. Nanotechnology can be used to solve the
problems associated with these conventional approaches
for solubility and bioavailability enhancement.
Nanosuspension is favored for compounds that are
insoluble in water (but are soluble in oil) with high log P
value, high melting point and high doses. Nanosuspension
technology can also be used for drugs which are insoluble
in both water and organic solvents. Hydrophobic drugs
13
14
15
such as Atorvastatin,
Famotidine,
Simvastatin,
are
formulated
as
Nanosuspensions are colloidal dispersions of nanosized
drug particles stabilized by surfactants. They can also be
defined as a biphasic system consisting of pure drug
particles dispersed in an aqueous vehicle in which the
diameter of the suspended particle is less than 1µm in
size. The Nanosuspensions can also be lyophilized or
spray dried and the nanoparticles of a Nanosuspension
can also be incorporated in a solid matrix18-23.
Nano is a Greek word, which means ‘dwarf’. Nano means
it is the factor of 10-9 or one billionth. Some comparisons
of nanoscale are given below,
0.1 nm
= Diameter of one Hydrogen atom.
2.5 nm
= Width of a DNA molecule
1 micron
= 1000 nm.
-9
-7
-6
1 nm = 10 m= 10 cm = 10 mm.
-6
-4
-3
Micron = 10 m= 10 cm = 10 mm 4.
For a long duration of time micronization of poorly
soluble drugs by colloid mills or jet mills was preferred.
The overall particle size distribution ranges from 0.1µm to
approximately 25µm, only negligible amount being below
1µm in the nanometer range.
When to go for Nano Suspensions Approach
 Preparing nano suspensions is preferred for the
compounds that are insoluble in water (but are
soluble in oil) with high log P value.
 Conventionally the drugs that are insoluble in water
but soluble in oil phase system are formulated in
liposome, emulsion systems but these lipidic
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Int. J. Pharm. Sci. Rev. Res., 22(1), Sep – Oct 2013; nᵒ 20, 98-106
formulation approaches are not applicable to all
drugs. In these cases nano suspensions are preferred.
 In case of drugs that are insoluble in both water and
in organic media instead of using lipidic systems
Nanosuspensions are used as a formulation
approach.
 Nanosuspension formulation approach is most
suitable for the compounds with high log P value,
high melting point and high dose.24,25
Potential Benefits of Nanosuspension Technology for
Poorly Soluble Drugs
 Reduced particle size, increased drug dissolution
rate, increased rate and extent of absorption,
increased bioavailability of drug, area under plasma
versus time curve, onset time, peak drug level,
reduced variability, reduced fed/fasted effects.
 Nanosuspensions can be used for compounds that
are water insoluble but which are soluble in oil. On
the other hand, Nanosuspensions can be used in
contrast with lipidic systems, successfully formulate
compounds that are insoluble in both water and oils.
 Nanoparticles can adhere to the gastrointestinal
mucosa, prolonging the contact time of the drug and
thereby enhancing its absorption.
 A pronounced advantage of Nanosuspension is that
there are many administration routes for
Nanosuspensions, such as oral, parenteral,
pulmonary, dermal and ocular.
 Nanosuspension of nanoparticles (NPs) offers various
advantages over conventional ocular dosage forms,
including reduction in the amount of dose,
maintenance of drug release over a prolonged period
of time, reduction in systemic toxicity of drug,
enhanced drug absorption due to longer residence
time of nanoparticles on the corneal surface, higher
drug concentrations in the infected tissue, suitability
for poorly water-soluble drugs and smaller particles
are better tolerated by patients than larger particles,
therefore nanoparticles may represent auspicious
drug carriers for ophthalmic applications.
 Nanosuspension has low incidence of side effects by
the excipients.
 Nanosuspensions overcome delivery issues for the
compounds by obviating the need to dissolve them,
and by maintaining the drug in a preferred crystalline
state of size sufficiently small for pharmaceutical
acceptability.
 Increased resistance to hydrolysis and oxidation,
increased physical stability to settling.
 Reduced administration volumes; essential for
intramuscular, subcutaneous, ophthalmic use.
 Finally, Nanosuspensions can provide the passive
26-29
targeting.
METHODS OF PREPARATION OF NANOSUSPENSION
Mainly there are two methods for preparation of
Nanosuspensions. The conventional methods of
precipitation (Hydrosols) are called ‘Bottom up
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technology’. The ‘Top Down Technologies’ are the
disintegration methods and are preferred over the
precipitation methods. The ‘Top Down Technologies’
include Media Milling (Nanocrystals), High Pressure
Homogenization in water (Dissocubes), High Pressure
Homogenization in non aqueous media (Nanopure) and
combination of Precipitation and High-Pressure
Homogenization (Nanoedege).22-29
1) Bottom-up technology
2) Top-down technology
Bottom-Up Technology
The term “Bottom-up technology” means that one starts
from the molecular level, and goes via molecular
association to the formation of a solid particle.That
means that we are discussing classical precipitation
techniques by reducing the solvent quality, for example,
by pouring the solvent into a nonsolvent or changing the
temperature or a combination of both. Precipitation is a
classical technique in pharmaceutical chemistry and
technology.30-34
Advantage
1) Use of simple and low cost equipment.
2) Higher saturation solubility is the advantage for
precipitation compared to other methods of
Nanosuspension preparation.
Disadvantages
1) The drug needs to be soluble in at least one solvent
(thus excluding all new drugs that are simultaneously
poorly soluble in aqueous and in organic media).
2) The solvent needs to be miscible with at least one nonsolvent.
3) Solvent residues need to be removed, thus increasing
production costs.
4) It is an Iittle bit tricky to preserve the particle character
(i.e. size, especially the amorphous fraction). In general, it
is recommended that a second consecutive process has to
be performed for particle preservation that is spray
drying or lyophilization35-37
Top-Down Technology
The top down technologies include
a) Media milling
b) High pressure homogenization
Media Milling
Nanosuspensions are produced by using high-shear media
mills or pearl mills. The mill consists of a milling chamber,
milling shaft and a recirculation chamber. An aqueous
suspension of the drug is then fed into the mill containing
small grinding balls/pearls. As these balls rotate at a very
high shear rate under controlled temperature, they fly
through the grinding jar interior and impact against the
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sample on the opposite grinding jar wall. The combined
forces of friction and impact produce a high degree of
particle size reduction. The milling media or balls are
made of ceramic-sintered aluminium oxide or zirconium
oxide or highly cross-linked polystyrene resin with high
abrasion resistance. Planetary ball mills (PM100 and
PM200; Retsch GmbH and Co., KG, Haan, Germany) is one
example of an equipment that can be used to achieve a
grind size below 0.1 µm. A Nanosuspension of Zn-Insulin
with a mean particle size of 150 nm was prepared using
the wet milling technique. The major drawbacks of this
technology include the erosion of balls/pearls that can
leave residues as contaminants in the final product,
degradation of the thermolabile drugs due to heat
generated during the process and presence of relatively
38-41
high proportions of particles ≥5 µm.
Advantages
 Simple technology
 Low-cost process regarding the milling itself
 Large-scale production possible to some extent
(batch process).
Disadvantages
 Potential erosion from the milling material leading to
product contamination.
 Duration of the process not being very production
friendly.
 Potential growth of germs in the water phase when
milling for a long time.
 Time and costs associated with the separation
procedure of the milling material from the drug
nanoparticle suspension, especially when producing
parenteral sterile products.38-41
High Pressure Homogenization
Dissocubes
Homogenization involves the forcing of the suspension
under pressure through a valve having a narrow aperture.
Dissocubes was developed by Muller et al. in 1999. In this
case, the suspension of the drug is made to pass through
a small orifice that result in a reduction of the static
pressure below the boiling pressure of water, which leads
to boiling of water and formation of gas bubbles. When
the suspension leaves the gap and normal air pressure is
reached again, the bubbles implode and the surrounding
part containing the drug particles rushes to the center
and in the process colloids, causing a reduction in the
particle size. Most of the cases require multiple passes or
cycles through the homogenizer, which depends on the
hardness of drug, the desired mean particle size and the
required homogeneity. This principle is employed in the
APV Gaulin Micron LAB 40 Homogenizer (APV
Homogenizer, Lόbeck, Germany) and the NS 1001L-Panda
2K high-pressure homogenizer (Nirosuavi. S.P.A., Parma,
Italy).
To produce a Nanosuspension with a higher
concentration of solids, it is preferred to start
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homogenization with very fine drug particles, which can
be accomplished by pre-milling. The major advantage of
high- pressure homogenization over media milling is that
it can be used for both diluted as well as concentrated
42-45
suspensions and also allows aseptic production.
Nanopure
Nanopure is suspensions homogenized in water-free
media or water mixtures. In the Dissocubes technology,
the cavitation is the determining factor of the process.
But, in contrast to water, oils and oily fatty acids have
very low vapour pressure and a high boiling point. Hence,
the drop of static pressure will not be sufficient enough to
initiate cavitation. Patents covering disintegration of
polymeric material by high- pressure homogenization
mention that higher temperatures of about 800C
promoted disintegration, which cannot be used for
thermolabile compounds. In nanopure technology, the
drug suspensions in the non- aqueous media were
homogenized at 00C or even below the freezing point and
hence are called "deep-freeze" homogenization. The
results obtained were comparable to Dissocubes and
hence can be used effectively for thermolabile substances
at milder conditions.46,47
Nanoedge™
The basic principles of Nanoedge are the same as that of
precipitation and homogenization. A combination of
these techniques results in smaller particle size and better
stability in a shorter time. The major drawback of the
precipitation technique, such as crystal growth and longterm stability, can be resolved using the Nanoedge
technology. In this technique, the precipitated suspension
is further homogenized; leading to reduction in particle
size and avoiding crystal growth. Precipitation is
performed in water using water-miscible solvents such as
methanol, ethanol and isopropanol. It is desirable to
remove those solvents completely, although they can be
tolerated to a certain extent in the formulation. For an
effective production of Nanosuspensions using the
Nanoedge technology, an evaporation step can be
included to provide a solvent-free modified starting
48
material followed by high-pressure homogenization.
Emulsion Diffusion Method
Apart from the use of emulsion as drug delivering vehicle
they can also be used as templates to produce
Nanosuspension. The use of emulsions as templates is
applicable for those drugs that are soluble in either
volatile organic solvent or partially water-miscile solvent.
Such solvents can be used as the dispersed phase of the
emulsion. An organic solvent or mixture of solvents
loaded with the drug is dispersed in the aqueous phase
containing suitable surfactants with stirring to form an
emulsion. The obtained emulsion was further
homogenized by high pressure homogenization. After
homogenization cycles the emulsion was diluted with
water, homogenized by homogenizer to diffuse the
organic solvent and convert the droplets into solid
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particles. Since one particle is formed in each emulsion
droplet, it is possible to control the particle size of the
Nanosuspension by controlling the size of the emulsion
optimizing the surfactant composition increases the
intake of organic phase and ultimately the drug loading in
the emulsion. Originally methanol, ethanol, ethyl acetate
chloroform are used as a organic solvents.47-50
Advantages
 Use of specialized equipment is not necessary.
 Particle size can easily be controlled by controlling
the size of the emulsion droplet.
 Ease of scale-up if formulation is optimized properly.
Disadvantages
 Drugs that are poorly soluble in both aqueous and
organic media cannot be formulated by this
technique.
 Safety concerns because of the use of hazardous
solvents in the process.
 Need for diultrafiltration for purification of the drug
Nanosuspension, which may render the process
costly.
 High amount of surfactant/stabilizer is required as
compared to the production techniques described
earlier.47-50
Micro emulsion Template
This technique follows an organic solvent or mixture
solvent loaded with the drug dispersed in an aqueous
phase containing suitable surfactants to form an
emulsion. The organic phase is then evaporated under
reduced pressure to make drug particles precipitate
instantaneously to form the Nanosuspension which is
stabilized by surfactants. Another method makes use of
partially water-miscible solvents such as butyl lactate,
benzyl alcohol and triacetin as the dispersed phase
instead of hazardous solvents.48-51
Advantages
 Use of specialized equipment is not necessary.
 Particle size can easily be controlled by controlling
the size of the emulsion droplet.
 Ease of scale-up if formulation is optimized properly.
Disadvantages
 Drugs that are poorly soluble in both aqueous and
organic media cannot be formulated by this
technique.
 Need for diultrafiltration for purification of the drug
Nanosuspension, which may render the process
costly.
 High amount of surfactant/stabilizer is required as
compared to the production techniques described
earlier.
Supercritical Fluid Method
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attempted are rapid expansion of supercritical solution
process (RESS), supercritical anti-solvent process and
precipitation with compressed anti-solvent process
(PCA).The RESS involves expansion of the drug solution in
supercritical fluid through a nozzle, which leads to loss of
solvent power of the supercritical fluid resulting in
precipitation of the drug as fine particles. Young et
al. prepared cyclosporine nanoparticles in the size range
of 400-700 nm using this process. In the PCA method, the
drug solution is atomized into a chamber containing
compressed CO 2 . As the solvent is removed, the solution
gets supersaturated and thus precipitates as fine crystals.
The supercritical anti- solvent process uses a supercritical
fluid in which a drug is poorly soluble and a solvent for
the drug that is also miscible with the supercritical fluid.
The drug solution is injected into the supercritical fluid
and the solvent gets extracted by the supercritical fluid
and the drug solution gets supersaturated. The drug is
then precipitated as fine crystals. Nanoparticles of
griseofulvin, a drug with poor solubility, were prepared by
Chattopadhyay et al. using this method.46-51
Disadvantages
 Use of hazardous solvents and use of high
proportions of surfactants and stabilizers as
compared with other techniques,
 Particle nucleation overgrowth due to transient high
super saturation, which may also result in the
development of an amorphous form or another
undesired polymorph.
Melt emulsification method
In this method drug is dispersed in the aqueous solution
of stabilizer and heated above the melting point of the
drug and homogenized to give an emulsion. During this
process, the sample holder was enwrapped with a
heating tape fitted with temperature controller and the
temperature of emulsion was maintained above the
melting point of the drug. The emulsion was then cooled
down either slowly to room temperature or on an icebath50,51
Advantage
Melt emulsification technique relative to the solvent
diffusion method is total avoidance of organic solvents
during the production process.
Dry Co-Grinding
Recently, Nanosuspensions can be obtained by dry milling
techniques. Successful work in preparing stable
Nanosuspensions using dry-grinding of poorly soluble
drugs with soluble polymers and copolymers after
dispersing in a liquid media has been reported. Many
soluble polymers and co-polymers such as PVP,
polyethylene glycol (PEG), hydroxypropyl methylcellulose
51,52
(HPMC) and cyclodextrin derivatives have been used.
Supercritical fluid technology can be used to produce
nanoparticles from drug solutions. The various methods
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Formulation Consideration
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nanosuspension and moisture content of dried nanosized
drug should be given due consideration.53,54
Stabilizer
The main function of a stabilizer is to wet the drug
particles thoroughly, and to prevent ostwald’s ripening
and agglomeration of Nanosuspensions in order to yield a
physically stable formulation by providing steric or ionic
barrier. The type and amount of stabilize has a
pronounced effect on the physical stability and in vivo
behavior of Nanosuspension. Stabilizers that have been
used so far are poloxomers, polysorbate, cellulosics,
povidones, and lecithins.
Lecithin is the stabilizer of choice if one intends to
develop a parentally acceptable and autoclavable
nanosuspension.52
Organic Solvent
Organic solvents are used in the formulation of
Nanosuspension if emulsions or micro emulsions are used
as a template. The pharmaceutically acceptable less
hazardous water miscible solvent, such as methanol,
ethanol, chloroform, ispropanol, and partially water
miscible solvents ethyl acetate, ethyl formate, butyl
lactate, triacetin, propylene carbonate, benzyl alcohol,
are preferent in the formulation over the conventional
hazardous solvents, such as dichloromethane.52,53
Co-Surfactants
The choice of co-surfactant is critical when using micro
emulsions to formulate Nanosuspensions. Since cosurfactants can greatly influence phase behaviour, the
effect of co-surfactant on uptake of the internal phase for
selected micro emulsion composition and on drug loading
should be investigated. Although the literature describes
the use of bile salts and dipotassium glycerrhizinate as cosurfactants, various solubilizers, such as Transcutol,
glycofurol, ethanol and isopropanol, can be safely used as
co-surfactants in the formulation of microemulsions.54
Other additives
Nanosuspensions may contain additives such as buffers,
salts, polyols, osmogent and cryoprotectant.
Post-Production Processing
Post-production processing of Nanosuspensions becomes
essential when the drug candidate is highly susceptible to
hydrolytic cleavage or chemical degradation. Processing
may also be required when the best possible stabilizer is
not able to stabilize the Nanosuspension for a longer
period of time or there are acceptability restrictions with
respect to the desired route. Considering these aspects,
techniques such as lyophilization or spray drying may be
employed to produce a dry powder of nano-sized drug
particles. Rational selection has to be made in these unit
operations considering the drug properties and economic
aspects. Generally, spray drying is more economical and
convenient than lyophilization. The effect of postproduction processing on the particle size of the
Characterization of Nanosuspension1-54
In-vitro evaluations










Color, Odor, Taste
Particle size distribution
Particle charge (Zeta Potential)
Crystal morphology
Dissolution velocity and Saturation solubility
Density
pH Value
Droplet Size
Viscosity Measurement
Stability of Nanosuspension
In-vivo Biological Performance
Evaluation for surface-modified Nanosuspension



Surface hydrophilicity
Adhesion properties
Interaction with body proteins
In-vitro evaluations

Color, Odor, Taste
These characteristics are especially important in orally
administered formulation. Variations in taste, especially
of active constituents, can offered be attributed to
changes in particle size, crystal habit and subsequent
particle dissolution. Changes in color, odor and taste can
also indicate chemical instability.

Particle Size Distribution
Particle size distribution determines the physiochemical
behavior of the formulation, such as saturation solubility,
dissolution velocity, physical stability, etc. The particle
size distribution can be determined by photon correlation
spectroscopy (PCS), laser diffraction (LD) and coulter
counter multisizer. The PCS method can measure particles
in the size range of 3 nm to 3µm and the LD method has a
measuring range of 0.05-80µm. The coulter counter
multisizer gives the absolute number of particles, in
contrast to the LD method, which gives only a relative size
distribution. For IV use, particles should be less than 5µm,
considering that the smallest size of the capillaries is 56µm and hence a higher particle size can lead to capillary
blockade and embolism.

Zeta Potential
Zeta potential is an indication of the stability of the
suspension. For a stable suspension stabilized only by
electrostatic repulsion, a minimum zeta potential of ±30
mV is required whereas in case of a combined
electrostatic and steric stabilizer, a zeta potential of ±20
mV would be sufficient.
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
Crystal Morphology

To characterize the polymorphic changes due to the
impact of high-pressure homogenization in the crystalline
structure of the drug, techniques like X-ray diffraction
analysis in combination with differential scanning
calorimetry or differential thermal analysis can be
utilized. Nanosuspensions can undergo a change in the
crystalline structure, which may be to an amorphous form
or to other polymorphic forms because of high-pressure
homogenization.

Dissolution Velocity and Saturation Solubility
Nanosuspensions have an important advantage over
other techniques, that it can increase the dissolution
velocity as well as the saturation solubility. These two
parameters should be determined in various physiological
solutions. The assessment of saturation solubility and
dissolution velocity helps in determining the in
vitro behavior of the formulation. Böhm et al. reported an
increase in the dissolution pressure as well as dissolution
velocity with a reduction in the particle size to the
nanometer range. 17 Size reduction leads to an increase in
the dissolution pressure.

Density
Specific gravity or density of the formulation is an
important parameter. A decrease in density often
indicates the presence of entrapped air within the
structure of the formulation. Density measurements at a
given temperature should be made using well mixed,
uniform formulation; precision hydrometer facilitate such
measurements.

pH Value
The pH value of aqueous formulation should be taken at a
given temperature and only after settling equilibrium has
been reached, to minimize “pH drift” and electrode
surface coating with suspended particles. Electrolyte
should not be added to the external phase of the
formulation to stabilized the pH.

Droplet Size
The droplet size distribution of micro emulsion vesicles
can be determined by either light scattering technique or
electron microscopy. Dynamic light scattering
spectrophotometer which uses a neon laser of
wavelength 632 nm.

Viscosity Measurement
The viscosity of lipid based formulations of several
compositions can be measured at different shear rates at
different temperatures using Brookfield type rotary
viscometer. The sample room of the instrument must be
maintained at 370C by a thermo bath and the samples, for
the measurement are to be immersed in it.
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Stability of Nanosuspension
The high surface energy of nanosized particles induces
agglomeration of the drug crystals. The main function of
the stabilizer is to wet the drug particles thoroughly to
prevent Ostwald ripening and agglomeration of the
Nanosuspension and form a physically stable formulation
by providing a steric or an ionic barrier. Typical examples
of stabilizers used in Nanosuspensions are cellulosics,
poloxamer, polysorbates, lecithin, polyoleate and
povidones. Lecithin may be preferred in developing
parenteral Nanosuspensions.
In-Vivo Biological Performance
The establishment of an in-vitro/in-vivo correlation and
the monitoring of the in-vivo performance of the drug is
an essential part of the study, irrespective of the route
and the delivery system employed. It is of the utmost
importance in the case of intravenously injected
Nanosuspensions since the in-vivo behavior of the drug
depends on the organ distribution, which in turn depends
on its surface properties, such as surface hydrophobicity
and interactions with plasma proteins In fact, the
qualitative and quantitative composition of the protein
absorption pattern observed after the intravenous
injection of nanoparticles is recognized as the essential
factor for organ distribution. Hence, suitable techniques
have to be used in order to evaluate the surface
properties and protein interactions to get an idea of invivo behavior. Techniques such as hydrophobic
interaction chromatography can be used to determine
surface hydrophobicity, whereas 2-D PAGE can be
employed for the quantitative and qualitative
measurement of protein adsorption after intravenous
injection of drug nanosuspensions in animals.
APPLICATIONS OF NANOSUSPENSIONS
Oral
Oral drug delivery is the most widely preferred route of
administration of drugs. But, some drugs possess the
problem of limited bioavailability due to poor solubility
and absorption which ultimately reduces its efficacy. In
such cases, Nanosuspension can solve the problem as it
helps in improving the dissolution rate and absorption
due to increased surface area and enhanced
adhesiveness. Nanosuspension can lead to increased
mucoadhesion which can increase gastrointestinal transit
time and lead to increased bioavailability. The
enhancement in oral bioavailability can be attributed to
increased surface area, saturation solubility and the
adhesiveness of the drug Nanosuspension. Taste masking
of particulate system is also easily possible.
Parenteral
Nanosuspensions can be used to transform poorly soluble
non-injectable drugs into a formulation suitable for
intravenous administration. Although the production of
Nanosuspension for parenteral use is critical, current
developments in this technology have proved its utility as
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injectable formulations. The methods used for
preparation of Nanosuspension are now precisely
controlled, and are able to produce uniform particles with
better control over maximum particle size. Various
research reports are available which emphasize the
applicability of Nanosuspensions for parenteral
administration.
Ocular delivery
Nanosuspension can prove to be a boon for drugs that
exhibit
poor
solubility
in
lachrymal
fluids.
Nanosuspensions represent an ideal approach for ocular
delivery of hydrophobic drugs due to their inherent ability
to improve saturation solubility of drugs. Kassem et al.,
have developed Nanosuspension delivery system for
certain glucocorticoid drugs
Pulmonary
Nanosuspensions can be advantageous for delivering
drugs that exhibit poor solubility in pulmonary secretion.
Currently available approaches for pulmonary delivery
such as aerosols or dry powder inhalers possess certain
disadvantages such as limited diffusion at required site,
less residence time etc, which can be overcome by
Nanosuspensions. Fluticasone and budesonide have been
successfully formulated as Nanosuspension for
pulmonary Delivery.
Dermal
The nanocrystalline form possesses increased saturation
solubility resulting in enhanced diffusion of the drug into
the skin. Nanocrystals also exhibit various properties such
as increased penetration into a membrane, enhanced
permeation and bioadhesiveness which could be very
useful for dermal application.
Targeting
The uptake of drug nanoparticles depends on their
particle size. By changing the surface properties of the
nanoparticles, their in vivo behavior can be altered and
can be used as targeted delivery system. The
phagocytotic uptake of nanocrystals can be avoided by
preparing stealth nanocrystals or by preparing smart
crystals i.e. drug particles below particle size of 100nm,
which can be used as a targeted drug delivery system.
Due
to method simplicity, development of
nanosuspension is a commercially viable option for
targeted delivery. Mucoadhesive nanosuspension was
reported for targeting of Cryptosporidium parvum. The
surface properties of particles such as surface
hydrophobicity, charge, presence and concentration of
certain functional groups determine its organ distribution.
Thus, Tween 80 coated nanocrystals can be used for brain
targeting. Atovaquone nanocrystals coated with Tween
80 were used to treat toxoplasmosis; the parasites could
be efficiently eradicated in brain.
ISSN 0976 – 044X
Mucoadhesion of the Nanoparticles
Nanoparticles orally administered in the form of a
suspension diffuse into the liquid media and rapidly
encounter the mucosal surface. The particles are
immobilized at the intestinal surface by an adhesion
mechanism referred to as "bioadhesion." From this
moment on, the concentrated suspension acts as a
reservoir of particles and an adsorption process takes
place very rapidly. The direct contact of the particles with
the intestinal cells through a bioadhesive phase is the first
step before particle absorption.
Table 1: Marketed Products
Product
Drug
Indication
Company
Triglide
Fenofibrate
Treatment of
hypercholestero
lemia
First horizon
pharmaceut
ical
Tricor
Fenofibrate
Treatment of
hypercholestero
lemia
Abbott
Megace
Megestrol
aceyate
Appetite
stimulant
PARPharma
ceutical
Rapamune
sirolimus
Immunosuppres
ant
Wyeth
Future Prospects
Nanosuspension technology is a unique and novel
approach to overcome drug problems such as poor
bioavailability that are related with the delivery of
hydrophobic drugs, including those that are poorly
soluble in aqueous as well as organic media. Production
methods like media milling and high-pressure
homogenization have been successfully employed for
large
scale
production
of
Nanosuspensions.
Nanosuspension technology can be combined with
traditional dosage forms: tablets, capsules, pellets, and
can be used for parenteral products. To take advantage of
Nanosuspension drug delivery, simple formation
technologies and variety applications, Nanosuspensions
will continue to be of interest as oral formulations and
non-oral administration develop in the future. In
consideration to data available Nanosuspensions can be
considered as renaissance in formulation technologies for
coming years.
CONCLUSION
Nanosuspension solved poor bioavailability problem of
hydrophobic drugs and drugs which are poorly soluble in
aqueous and organic solutions. Productions techniques
such as media milling and high pressure homogenizer are
used for large scale production of Nanosuspensions.
Nanosuspensions can be administered through oral,
parenteral, pulmonary, ocular and topical routes. Since
nanotechnique is simple, less requirements of excipients,
increased dissolution velocity and saturation solubility
many poor bioavailability drugs are formulated in
Nanosuspension form.
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104
Int. J. Pharm. Sci. Rev. Res., 22(1), Sep – Oct 2013; nᵒ 20, 98-106
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